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Background <p>Efsubaglutide alfa, as a novel glucagon-like peptide-1 receptor agonist, was developed for the treatment of type 2 diabetes mellitus. Its effect on the rate and extent of absorption of concomitant oral medications (digoxin and metformin) was evaluated in healthy participants.</p> Methods <p>We conducted a single-center, open-label, fixed-sequence clinical trial involving 32 healthy participants who were assigned to either digoxin (<i>N</i> = 16) or metformin (<i>N</i> = 16) groups. The participants received oral doses of digoxin (0.25 mg, single dose) or metformin (1000 mg at first dose, 500 mg twice daily for 2 days) before and after subcutaneous injections of 3 mg efsubaglutide alfa at steady state. Pharmacokinetic parameters of digoxin and metformin before and after the administration of efsubaglutide alfa injections were measured, and safety assessments were conducted throughout the study.</p> Results <p>Efsubaglutide alfa slightly delayed the time to reach peak plasma concentration (<i>T</i><sub>max</sub>) of digoxin but had no substantial effect on its elimination. While the maximum concentration (<i>C</i><sub>max</sub>) of digoxin decreased by approximately 24% (from 1.75 ± 0.673 to 1.37 ± 0.545 ng/mL), and AUC<sub>0–inf</sub> increased by about 15% (from 20.2 ± 3.53 to 23.2 ± 4.04 ng/h/mL). In the metformin group, efsubaglutide alfa did not noticeably affect <i>T</i><sub>max</sub>, <i>C</i><sub>max,ss</sub>, or the overall pharmacokinetics, as demonstrated by a consistent AUC<sub>0–tau</sub> (from 7557 ± 2155 to 8737 ± 2852 ng/h/mL). Adverse events with efsubaglutide alfa and co-administered medication were comparable to those reported during treatment with efsubaglutide alfa alone and were mostly gastrointestinal-related.</p> Conclusions <p>No clinically significant pharmacokinetic change of digoxin and metformin was identified, and no new safety issues were observed with the co-administration of efsubaglutide alfa injection. These findings suggest that no dose adjustments are required for digoxin and metformin when co-administration with efsubaglutide alfa.</p> ClinicalTrials.gov Identifier <p>NCT05694221.</p>

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Effect of Efsubaglutide Alfa on the Pharmacokinetics of Metformin and Digoxin in Healthy Participants

  • 期刊论文

  • 发表日期：

    2025年6月30日

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  • Xiaojie Wu,
  • Jinjie He,
  • Junzhen Wu,
  • Wei Liu,
  • Yulong Xu,
  • Yiming Li,
  • Jing Zhang,
  • Qinghua Wang

摘要

Background

Efsubaglutide alfa, as a novel glucagon-like peptide-1 receptor agonist, was developed for the treatment of type 2 diabetes mellitus. Its effect on the rate and extent of absorption of concomitant oral medications (digoxin and metformin) was evaluated in healthy participants.

Methods

We conducted a single-center, open-label, fixed-sequence clinical trial involving 32 healthy participants who were assigned to either digoxin (N = 16) or metformin (N = 16) groups. The participants received oral doses of digoxin (0.25 mg, single dose) or metformin (1000 mg at first dose, 500 mg twice daily for 2 days) before and after subcutaneous injections of 3 mg efsubaglutide alfa at steady state. Pharmacokinetic parameters of digoxin and metformin before and after the administration of efsubaglutide alfa injections were measured, and safety assessments were conducted throughout the study.

Results

Efsubaglutide alfa slightly delayed the time to reach peak plasma concentration (Tmax) of digoxin but had no substantial effect on its elimination. While the maximum concentration (Cmax) of digoxin decreased by approximately 24% (from 1.75 ± 0.673 to 1.37 ± 0.545 ng/mL), and AUC0–inf increased by about 15% (from 20.2 ± 3.53 to 23.2 ± 4.04 ng/h/mL). In the metformin group, efsubaglutide alfa did not noticeably affect Tmax, Cmax,ss, or the overall pharmacokinetics, as demonstrated by a consistent AUC0–tau (from 7557 ± 2155 to 8737 ± 2852 ng/h/mL). Adverse events with efsubaglutide alfa and co-administered medication were comparable to those reported during treatment with efsubaglutide alfa alone and were mostly gastrointestinal-related.

Conclusions

No clinically significant pharmacokinetic change of digoxin and metformin was identified, and no new safety issues were observed with the co-administration of efsubaglutide alfa injection. These findings suggest that no dose adjustments are required for digoxin and metformin when co-administration with efsubaglutide alfa.

ClinicalTrials.gov Identifier

NCT05694221.